Combining Patulin with Cadmium Induces Enhanced Hepatotoxicity and Nephrotoxicity In Vitro and In Vivo.
Combining Patulin with Cadmium Induces Enhanced Hepatotoxicity and Nephrotoxicity In Vitro and In Vivo.
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DOI：
10.3390/toxins13030221
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发表时间：
2021-03-18
期刊：
影响因子：
4.2
通讯作者：
Hu H
中科院分区：
文献类型：
--
作者：
Cui J;Yin S;Zhao C;Fan L;Hu H
食物可能被各种类型的污染物污染，如霉菌毒素和有毒重金属。因此，消费者很可能同时摄入一种以上的食物污染物，这为研究这些食物污染物的联合毒性提供了强有力的理由。棒曲霉素是最常见的食源性真菌毒素之一，而镉是食物中有毒重金属的代表。肝脏和肾脏是棒曲霉素和镉的主要靶器官部位。我们假设同时暴露于棒曲霉素和镉可以产生协同肝毒性和肾毒性。采用小鼠肝细胞系12（AML 12）和人胚肾细胞系293（HEK 293）与小鼠模型，探讨联合效应和机制。结果表明，第一次，肝或肾细胞共同暴露于棒曲霉素和镉引起协同细胞毒性在体外和增强肝毒性在体内。棒曲霉素和镉联合给药引起的协同毒性归因于活性氧（ROS）的产生增加。c-Jun N末端激酶1（JNK 1）和p53作为氧化应激的下游介质，参与了棒曲霉素和镉联合暴露的协同毒性，而p53/JNK 1的激活通过正反馈回路促进了第二轮ROS的产生。本研究的发现扩展了关于棒曲霉素和镉的毒理学知识，这可能有助于更准确地对这些食品污染物进行风险评估。
Food can be contaminated by various types of contaminants such as mycotoxins and toxic heavy metals. Therefore, it is very likely that simultaneous intake of more than one type of food contaminant by consumers may take place, which provides a strong rationale for investigating the combined toxicities of these food contaminants. Patulin is one of the most common food-borne mycotoxins, whereas cadmium is a representative of toxic heavy metals found in food. The liver and kidneys are the main target organ sites for both patulin and cadmium. We hypothesized that simultaneous exposure to patulin and cadmium could produce synergistic hepatotoxicity and nephrotoxicity. Alpha mouse liver 12 (AML12) and Human embryonic kidney (HEK) 293 (HEK293) cell lines together with a mouse model were used to explore the combination effect and mechanism. The results demonstrated, for the first time, that the co-exposure of liver or renal cells to patulin and cadmium caused synergistic cytotoxicity in vitro and enhanced liver toxicity in vivo. The synergistic toxicity caused by the co-administration of patulin and cadmium was attributed to the boosted reactive oxygen species (ROS) generation. c-Jun N-terminal kinase 1 (JNK1) and p53 as downstream mediators of oxidative stress contributed to the synergistic toxicity by co-exposure of patulin and cadmium, while p53/JNK1 activation promoted the second-round ROS production through a positive feedback loop. The findings of the present study extend the toxicological knowledge about patulin and cadmium, which could be beneficial to more precisely perform risk assessments on these food contaminants.
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影响因子：
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